Conjugation of the T1 sequence from CCN1 to fibrin hydrogels for therapeutic vascularization
| Autor: | Isabel F. Amaral, Cristina C. Barrias, Paulo Aguiar, Joana A. Loureiro, Ana Luísa Torres, Marta Pinto, Tânia Neto |
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| Rok vydání: | 2019 |
| Předmět: |
Materials science
Cell Survival Central nervous system Integrin Neovascularization Physiologic Bioengineering 02 engineering and technology 010402 general chemistry 01 natural sciences Chorioallantoic Membrane Fibrin Cell Line Biomaterials chemistry.chemical_compound In vivo medicine Animals Humans Inducer Viability assay Cell Proliferation biology Viscosity Endothelial Cells Hydrogels 021001 nanoscience & nanotechnology Elasticity 0104 chemical sciences Cell biology Vascular endothelial growth factor medicine.anatomical_structure chemistry Mechanics of Materials Self-healing hydrogels biology.protein 0210 nano-technology Chickens Cysteine-Rich Protein 61 |
| Zdroj: | Materials Science and Engineering: C. 104:109847 |
| ISSN: | 0928-4931 |
| DOI: | 10.1016/j.msec.2019.109847 |
| Popis: | Hydrogel matrices with angiogenic properties are much desirable for therapeutic vascularization strategies, namely to provide vascular supply to ischemic areas, transplanted cells, or bioengineered tissues. Here we report the pro-angiogenic effect of fibrin (Fb) functionalization with the T1 sequence from the angiogenic inducer CCN1, forseeing its use in the injured brain and spinal cord. Fibrin functionalization with 40 μM of T1 peptide effectively improved cellular sprouting of human brain microvascular endothelial cells (hCMEC/D3) in the absence of vascular endothelial growth factor (VEGF), without impacting the viscoelastic properties of Fb, cell viability, or proliferation. The pro-angiogenic effect of immobilized T1 was potentiated in the presence of VEGF and partially mediated through α6β1 integrin. The tethering of T1 also enhanced sprouting of human cord blood-derived outgrowth endothelial cells (OEC). Still, to elicit such effect, a higher input T1 concentration was required (60 μM), in line with the lower protein levels of α6 and β1 integrin subunits found in OEC comparing to hCMEC/D3, prior to embedment in Fb gel. Finally, the ability of T1-functionalized Fb in inducing cappilary invasion in vivo was assessed using the CAM assay, which evidenced a significant increase in the number of newly formed vessels at sites of implantation of T1-functionalized Fb, in the absence of soluble angiogenic factors. Overall these results demonstrate the potential of T1 peptide-presenting gels for use in therapeutic vascularization approaches. Considering T1 neurite-extension promoting capability and pro-angiogenic properties, T1-functionalized Fb hydrogels are particularly promising for application in the injured central nervous system. |
| Databáze: | OpenAIRE |
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